This invention relates to a process for encapsulating tissue or individual cells so that they remain viable and in a protected state within a membrane which is permeable to nutrients, ions, oxygen, and other materials needed to both maintain the tissue and support its normal metabolic functions, but impermeable to bacteria, lymphocytes, and large proteins of the type responsible for immuochemical reactions resulting in rejection. The process enables the production of, for example, an insulin producing system or other hormone producing system as it allows encapsulation of mammalian pancreatic beta cells, alpha cells, intact islets of Langerhans, and other tissues or tissue fractions which secrete hormones. The capsules may be suspended in a culture medium and will excrete hormone over an extended period. The capsules may also be used as an artificial pancreas which can be implanted, e.g., by injection, into a diabetic mammal and will function in vivo to excrete insulin and other hormones in response to ambient sugar concentration.
it is believed that the art is devoid of methods for encapsulating living tissue such that the tissue remains viable. Attempts to accomplish this are frustrated by the conditions required for capsular membrane formation which are typically hostile to living systems. Copending U.S. application Ser. No. 606,166, to F. Lim et al., filed Aug. 20, 1975, the disclosure of which is incorporated herein by reference, discloses a technique for encapsulating labile biological materials within a semipermeable membrane. This technique is capable, for example, of encapsulating enzymes within a membrane from which the enzyme cannot escape, while allowing free passage of the enzyme's substrate. However, while the technique involves reaction conditions which preserve the fragile operability of biological materials, no suggestion is made that living tissue can be encapsulated.
Encapsulated live cells, organelles, or tissue have many potential uses. For example, within a semipermeable membrane, the encapsulated living material can be preserved in a permanent sterile environment and can be shielded from direct contact with large, potentially destructive molecular species, yet will allow free passage of lower molecular weight tissue nutrients and metabolic products. Thus, the development of such an encapsulation technique could lead to systems for producing useful hormones such as insulin. In such systems, the mammalian tissue responsible for the production of the material would be encapsulated in a manner to allow free passage of nutrients and metabolic products across the membrane, yet prohibit the passage of bacteria. If membrane permeability could be controlled, it is possible that this approach could also lead to artificial organs which could be implanted in a mammalian body, e.g., a diabetic, without rejection and with controlled hormone release, e.g., insulin release triggered by glucose concentration.
Various attempts have been made to produce artificial organs suitable for implantation in mammalian bodies by providing a mechanical semipermeable barrier, e.g., a Millipore diffusion chamber or a capillary tube chamber, about tissue excised from a donor. Such artificial organs normally require surgical implantation. Furthermore, the protective mechanisms of mammalian bodies isolate the implant, typically by plugging pores by fibroblastic overgrowth.